1. Field of the Invention
This invention relates to the culturing of animal cells, and particularly it relates to an apparatus for culturing animal cells which makes it possible to measure and diagnose the activity status of animal cells under culturing while maintaining the physiological conditions of the animal cells, a culturing method and diagnostics of the culture.
2. The Related Art Statement
The production of new medical drugs by the culturing of animal cells gives as small an output as some ng-.mu.g/10.sup.6 cells.day. The improvement of the drug productivity requires (1) high densification of cells and formation of a high capacity apparatus and (2) achievement of high secretory activity of cells. In order to attain the above (2), it is necessary to measure activities of cells in a culture medium (survival, division, secretion, etc.) under the condition that the physiological conditions of the cells are maintained and the system is closed. However, under the present situation, it is general practice to determine proportions of living and dead cells according to a stain method in which a cell-staining agent is incorporated into a culture medium taken from a culturing vessel.
In the above stain method, a staining agent is incorporated, etc., i.e., the measurement cannot be made under the condition that the physiological conditions of cells are maintained, and it is therefore not possible to return the culture medium to the culturing vessel. Accordingly, the measurement system is under the open system and it is impossible to prevent infection of miscellaneous microorganisms, etc. The rate of proliferation of animal cells is as small as 1/100 of that of microorganisms. Hence, the inclusion of one microorganism in the culture system means an end of new drug production activity.
On the other hand, with regard to cells being cultured in a microscopically observable container such as a microplate, dish or culturing bottle, there is a proposal of a method by which to determine the status of cells, alive or dead, by image processing [Japanese Patent Kokai (laid-open) No. 201332/1987]. This method is applicable to species which is being cultured by using the above small containers. However, it is difficult to apply the above method to an apparatus of a practical culture scale.
Further, the above method is merely to determine the "living or dead" status of cells, and there is no industrial method to determine the activity status thereof at present.